PMID- 16234848
OWN - NLM
STAT- MEDLINE
DCOM- 20060518
LR  - 20161124
IS  - 0829-8211 (Print)
IS  - 0829-8211 (Linking)
VI  - 83
IP  - 5
DP  - 2005 Oct
TI  - Hypoxia inducible factor-1: regulation by nitric oxide in posthypoxic 
      microvascular endothelium.
PG  - 597-607
AB  - Microvascular endothelial cells provide a critical regulatory interface between 
      blood constituents and tissue. Hypoxia inducible factor-1 (HIF-1) is a key 
      transcription factor required for expression of hypoxia-dependent genes. We 
      employed a model of hypoxia and reoxygenation (H/R) using the dermal 
      microvascular endothelial cell line HMEC-1 to examine the effects of altered 
      oxygen concentrations on microvascular HIF-1 expression and nitric oxide (NO) 
      formation. Hypoxia increased inducible NO synthase (iNOS) mRNA in a 
      time-dependent manner in HMEC-1. However, endothelial NO synthase mRNA 
      progressively declined during hypoxia. H/R promoted significant increases in 
      cellular nitrite levels that were significantly abrogated by the specific iNOS 
      inhibitor N6-(1-iminoethyl)-L-lysine, di hy drochloride. Exogenous NO promoted 
      stabilization of the alpha subunit of HIF-1 and produced functional DNA binding. 
      Exposure of HMEC-1 to H/R resulted in previously unrecognized biphasic HIF-1alpha 
      stabilization during reoxygenation. When the iNOS gene was silenced through the 
      use of iNOS-specific small interfering RNA, HIF-1alpha stabilization and HIF-1 
      activation were dramatically diminished, suggesting that inducible NOS-derived NO 
      is a key factor sustaining HIF-1 activation during both hypoxia and 
      reoxygenation.
FAU - Natarajan, Ramesh
AU  - Natarajan R
AD  - Center for Vascular Inflammation Research, Division of Pulmonary and Critical 
      Care Medicine, Department of Internal Medicine, Box 980050, Virginia 
      CommonwealthUniversity, Richmond, VA 23298, USA. rnataraj@hsc.vcu.edu
FAU - Jones, Drew G
AU  - Jones DG
FAU - Fisher, Bernard J
AU  - Fisher BJ
FAU - Wallace, Timothy J
AU  - Wallace TJ
FAU - Ghosh, Shobha
AU  - Ghosh S
FAU - Fowler, Alpha A 3rd
AU  - Fowler AA 3rd
LA  - eng
GR  - HL-10355/HL/NHLBI NIH HHS/United States
GR  - R01-HL61359/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Canada
TA  - Biochem Cell Biol
JT  - Biochemistry and cell biology = Biochimie et biologie cellulaire
JID - 8606068
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (RNA, Messenger)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Cell Line
MH  - Electrophoretic Mobility Shift Assay
MH  - Endothelium, Vascular/enzymology/metabolism/*physiopathology
MH  - Gene Silencing
MH  - Humans
MH  - Hypoxia/*physiopathology
MH  - Hypoxia-Inducible Factor 1/genetics/metabolism/*physiology
MH  - Microscopy, Fluorescence
MH  - Nitric Oxide/*physiology
MH  - Nitric Oxide Synthase Type II/genetics
MH  - Protein Binding
MH  - Protein Transport
MH  - RNA Interference
MH  - RNA, Messenger/genetics
MH  - Transcription, Genetic
MH  - Transfection
EDAT- 2005/10/20 09:00
MHDA- 2006/05/19 09:00
CRDT- 2005/10/20 09:00
PHST- 2005/10/20 09:00 [pubmed]
PHST- 2006/05/19 09:00 [medline]
PHST- 2005/10/20 09:00 [entrez]
AID - o05-047 [pii]
AID - 10.1139/o05-047 [doi]
PST - ppublish
SO  - Biochem Cell Biol. 2005 Oct;83(5):597-607. doi: 10.1139/o05-047.